Comparison of DFS in vaccine treated patients and control patients [ Time Frame: 36 months ] [ Designated as safety issue: No ]

The primary objective is to compare the DFS in subjects with operable early-stage, node-positive breast cancer who receive standard of care multimodality therapy plus NeuVax™ as the treatment group or standard of care multimodality therapy plus the vaccine adjuvant, Leukine® as the control group.

Secondary Outcome Measures:

Assessment of DFS and OS at 3, 5 and 10 years in vaccine and control groups, respectively; assessment of safety [ Time Frame: 3 through 10 years ] [ Designated as safety issue: Yes ]

The secondary objectives are to evaluate the 2 groups of subjects for:

5- and 10-year DFS

3-year OS

5- and 10-year OS

Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)

E75 peptide acetate (HER2/neu p366-379) in WFI (1.5 mg/mL) mixed with 250 micrograms Leukine® (sargramostim, GM-CSF), will be administered in intradermal injections, in four divided doses (4 sites on upper thigh) once a month, for six consecutive months. At the end of the six months, NeuVax™ vaccine boosters will be given the same way once every six months for the next five times (totaling 36 months).

Other Name: E75 peptide acetate , WFI, sargramostim, GM-CSF

Active Comparator: Leukine®

Leukine® with WFI

Biological: Leukine® (sargramostim, GM-CSF) and water for injection

Leukine® 250 micrograms in water for injection, will be administered in intradermal injections, in four divided doses (4 sites on upper thigh) once a month, for six consecutive months. At the end of the six months, boosters inoculations will be given the same way once every six months for the next five times (totaling 36 months).

The subjects eligible for this trial have an early stage node-positive breast cancer. Their tumors express low or intermediate levels of the HER2 protein. NeuVax™ will be administered after completion of front-line, standard of care therapy (surgery, radiation therapy, and chemotherapy) and can be given concomitantly with physician prescribed endocrine treatment.

NeuVax™ is the immmunodominant nonapeptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTL) following binding to HLA-A2/A3 molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy through cell lysis HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. Based on a successful Phase 2 trial, which achieved its primary endpoint of DFS, the Food and Drug Administration (FDA) granted NeuVax a Special Protocol Assessment (SPA) for its Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) study.

The active portion of the study will last three years (36 months). The follow-up will last from 5 to 10 years.

Endpoints:

Primary efficacy endpoint:

3-year DFS

Secondary efficacy endpoints:

5- and 10-year DFS

3-year OS

5- and 10-year OS

Safety profile, and adverse events (AEs)

Patterns of recurrence to include Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)

Safety Assessments:

Subjects will be assessed at every study visit for the safety endpoints, AEs,vital signs, physical examinations and laboratory data; yearly follow-up of survival will include imaging studies, ECGs, MUGA or ECHO scans and concomitant medications.

Able and willing (or have legal representative) to understand the study and provide consent

Key Exclusion Criteria:

Bilateral breast malignancy or suspicious mass in opposite breast

Inflammatory breast malignancy

History of prior breast cancer, ductal carcinoma in situ

Prior trastuzumab therapy

New York Heart Association Stage 3 or 4 cardiac disease

Sensory/motor neuropathy ≥ Grade 2

Autoimmune diseases or immune deficiency disease

Subjects on chronic steroid therapy, other immunosuppressive therapy

Contacts and Locations

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For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01479244